Tumor specific or over-expressed antigens were detected on the surface of various cancer cells. e.g. HER2, specific MUC I, GM2 and MHC class II on melanoma cells. These and other markers may be used to target tumors, using specific antibodies, for example. Antibodies against tumor antigens were developed and are used in immunotherapy. Binding of antibodies to tumor, native or as carriers of various toxins may damage the tumor cells. Nevertheless, the number of cells in solid tumors is huge, and continue to proliferate and adjust to the treatment during the period of the treatment.
Innate immune responses may affect tumor mass, but in most cases they do not eliminate the progression of solid tumors. Recruiting specific immune cells and controlling desired responses could be performed by defined inducers. Macrophages maturate from monocytes and migrate to tissues, e.g. digestive tract, lung, blood vessels, liver. Neutrophils (polymorphonuclear cells) are present in the blood but not in normal tissues. Mostly, these cells of the innate immune system overcome infections, without help of the acquired arm. Macrophages arrive at the site of infection and attract large amounts of neutrophils. Both cell types identify pathogens through receptors which recognize molecules that are common to various alien pathogens. One of the major differences between pathogenic and non-pathogenic microorganisms is their ability to outperform the innate immune system. This is done in part of the cases by using polysaccharide capsules that mask the pathogen and is not identified by any of the macrophage receptors.
Receptors on different cells of the innate immune system allow fast response (hours) to pathogen (contrary to acquired immune response that takes days to develop). These receptors enable a diverse response. Some identify repeated structural motifs on the surface of pathogen, e.g. mannose receptor on macrophages. (but not monocytes or neutrophils), CD14 receptor to LPS and CD11/CD18 to glucan. A second type of receptors is characteristic of the complement and Fc of antibodies. These receptors allow identification and engulfment of particles that were detected and attached in sera to complement or antibodies. In addition there are receptors that induce movement towards a specific site (chemotaxis), e.g. f-Met-Leu-Phe bind to peptides N-formylated that are produced by bacteria. Another group of receptors induce effector molecules and influence the nature of the response, including concentration and activation of cells in the infected area.
An important factor in the macrophage-pathogen interaction is the release of cytokines that attract neutrophils and plasma proteins to initiate the inflammation process. Receptors that tag for the presence of a pathogen and stimulate expression of co-stimulatory molecules on macrophages and dendritic cells also stimulate the acquired immune response, including production of antibodies and activation of T cell lymphocytes.
An example for isolation of an inflammatory region can be found in Streptococci that trigger the induction of neutrophils that secrete mainly hyperperoxides. The response to the bacteria may among other effects preclude blood supply to the area and forms three radiuses: pus, inflammation and isolation. As the infection propagates, immune complexes may be released to the blood stream and cause a sepsis cascade. In immunotherapy, this may increase danger that the tumor may enter a necrotic, rather than apoptotic, procedure, causing sepsis. Therefore, the desired cascade is tumor elimination through an apoptotic procedure, rather than necrosis.
The inflammation response has three roles: 1. Transfer of molecules and cells to the infected region aimed at killing/eliminating the invader; 2. Formation of a finite border to prevent the spread of the infecting agent; 3. Fix damaged tissue.
Three processes take place at the inflammation site: 1. Enlargement of blood vessels and elevation in blood flow; 2. Expression of molecules that bind leukocytes; 3. Elevation in permeability of blood vessels, enabling migration of leukocytes. These processes are influenced by release of prostaglandins, leukotrienes, platelet activating factors followed by cytokines and chemokines by macrophages.
Monoclonal antibodies are able to target a single specific protein on cancer cells while minimizing collateral damage to healthy tissue that is caused by the toxicity associated with chemotherapy and radiation therapy. Since scientists were able to create monoclonal antibodies that could be safely used in humans, eight monoclonal antibodies have been approved for use in clinical treatments to trigger immune responses to cancer cells, modulate cancer cell growth, and deliver drugs to cancer cells. Of these, only three are used on solid tumors (85% of all cancers).
A major difficulty in developing monoclonal antibody treatments for solid tumors relates to their ability to penetrate the tumor. To be effective, the treatment must gain access to many viable cells within tumors at sufficient concentrations to effect a maximal change in the tumor. This is affected by several factors, including the characteristics of the tumor, the antibody, and the target. Recently, it has been shown that boosting the immune killer cells, it is possible to increase the antibody effectiveness against the tumor. T. Sato and K. Hasumi reported (Apr. 18, 2007, Annual Meeting of the American Association for Cancer Research in Los Angeles) that they were able to show in laboratory studies that adding NK cells expanded outside the body to a monoclonal antibody, Herceptin, which targets the HER2/neu protein on breast cancer cells, was more efficient at killing the cancer cells.